OXYGEN LEVELS AND RADIOSENSITIVITY IN TUMORS

描述：氧分压的定量、实时测量 体内和体外肿瘤将被用来确定缺氧的程度 以及它与辐射敏感性的关系。测量结果将 比较三种独立的测量组织中氧气的方法，聚焦 关于一种新的光学技术--磷光的氧依赖猝灭。 氧气水平和处理引起这些水平的变化，氧分压 组织中的分布(直方图)以及二维和三维地图 这些氧在组织中的分布都将被测量。三 重要的假设将得到检验。1.磷光测量许可证 利用血、氧异常分布检测小肿瘤 肿瘤内存在的压力。2.磷光 测量使量化氧分布成为可能。 并实时评估设计的干预措施的有效性 来改变这些氧气水平。3.组织中的氧分压是 对放射治疗和提高氧分压至关重要 肿瘤增加了一次辐射所杀死的细胞的比例。 我们的研究计划将：a.量化血液中的氧分压 在肿瘤和周围组织的生长和发育过程中 肿瘤的最新进展。B.量化肿瘤对氧的依赖反应 放射治疗及其对旨在改变肿瘤的干预措施的反应 新陈代谢和生理学。C.延长磷光猝灭时间 用不同的光学切片测量三维尺寸 激发光的波长，从而提高了分辨率 氧气和血液在血管系统中的分布。D.评估新的 生物材料中氧气测量用荧光粉，重点是 在近红外区吸收和磷化的那些 频谱。 正在对Pd-四苯并卟啉结构进行化学修饰以提供 可溶于水且校准不敏感的荧光粉 环境(pH、离子强度、白蛋白)的变化 浓度)。将选择可以注入的荧光粉 静脉注射，然后，在氧气测量后，由 肾脏。

DESCRIPTION: Quantitative, real time measurements of the oxygen pressure in tumors in vivo and in vitro will be used to determine the degree of hypoxia and its relationship to radiation sensitivity. The measurements will compare three independent methods for measuring oxygen in tissue, focusing on a new optical technique, oxygen dependent quenching of phosphorescence. O2 levels and treatment induced alterations in these levels, oxygen pressure distributions (histograms) in the tissue, and two and three dimensional maps of these oxygen distributions in the tissue will all be measured. Three important hypotheses will be tested. 1.Phosphorescence measurements permit detection of small tumors by the abnormal distributions of blood and oxygen pressures which are present within the tumors. 2. Phosphorescence measurements make it possible to quantitate the oxygen distribution in tumors and to evaluate, in real time, the efficacy of interventions designed to alter these oxygen levels. 3. The oxygen pressure in the tissue is critically important to radiation therapy and increased oxygen pressure in the tumor increases the fraction of cells killed by a dose of radiation. Our research program will: A. Quantitate the oxygen pressure in the blood within tumors and the surrounding tissue during the growth and development of the tumors. B. Quantitate the oxygen dependence of tumor response to radiation therapy and its response to interventions designed to alter tumor metabolism and physiology. C. Extend the phosphorescence quenching measurements to three dimensions by optically sectioning using different wavelengths of excitation light, thereby improving resolution of the distribution of oxygen and blood in the vasculature. D. Evaluate new phosphors for oxygen measurement in biological materials, with emphasis on those which absorb and phosphoresce in the near infra red region of the spectrum. The Pd-tetrabenzoporphyrin structure is being chemically modified to provide phosphors which are water soluble and with calibrations insensitive to alterations in their environment (pH, ionic strength, albumin concentration). Phosphors will be selected which can be injected intravenously and then, after the oxygen measurements, are excreted by the kidney.